Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation.
Level 3 - non-randomized controlled study
Non-randomized prospective before-and-after intervention study with a young comparison group
PubMed 21795440 · doi:10.3945/ajcn.110.003483
What was done
Eight elderly and eight younger individuals received stable-isotope infusions of [2H(2)]glycine to measure red blood cell (RBC) glutathione synthesis rates and concentrations, plasma oxidative stress, and oxidant damage markers (plasma F2-isoprostanes). Elderly participants were subsequently re-evaluated following two weeks of oral dietary supplementation with the glutathione precursors cysteine and glycine.
What was found
At baseline, elderly subjects compared with younger subjects had significantly lower RBC glycine (218.0 ± 23.7 vs 486.7 ± 28.3 μmol/L; P < 0.01), RBC cysteine (19.8 ± 1.3 vs 26.2 ± 1.4 μmol/L; P < 0.05), and RBC glutathione (1.12 ± 0.18 vs 2.08 ± 0.12 mmol/L RBCs; P < 0.05). Elderly subjects also had lower fractional synthesis rates (45.80 ± 5.69% vs 83.14 ± 6.43%/d; P < 0.01), lower absolute synthesis rates (0.55 ± 0.12 vs 1.73 ± 0.16 mmol/L RBCs/d; P < 0.01), higher plasma oxidative stress (346 ± 20 vs 304 ± 16 Carratelli units; P < 0.05), and higher plasma F2-isoprostanes (136.3 ± 11.3 vs 97.7 ± 8.3 pg/mL; P < 0.05). Following two weeks of precursor supplementation, elderly subjects experienced a 94.6% increase in RBC glutathione concentrations, a 78.8% higher fractional synthesis rate, and a 230.9% higher absolute synthesis rate, alongside significant reductions in plasma oxidative stress and F2-isoprostanes, eliminating baseline differences between the elderly and younger cohorts.
Why it matters
This study provides mechanistic evidence in humans that age-related glutathione depletion stems from impaired synthesis rather than increased clearance alone, and shows that oral precursor supplementation can rapidly restore synthesis rates and reduce systemic oxidative stress markers.
Limits
The sample size is very small (n = 8 per group). The study lacked a randomized placebo-controlled design for the intervention phase, had a brief duration of only two weeks, and evaluated solely circulating biochemical markers without measuring clinical or functional outcomes.
Cited by
- context Glutathione production declines naturally with age starting as early as in one's 20s.